ANTI-CHOLINERGIC DRUGS

Tropicamide

REF: khurana 4th ed p. 68

• shortest acting mydriatic – Tropicamide
• Only mydriatic and not cycloplegic – phenylephrine
• Used in children – Atropine

Floppy mitral valve REF: Pediatrics: A Concise Text – Text – SK Kabra, RN Srivastava Page 135

Repeat in December 2011

The murmur is the clinching point here as the patient is having ostium primum type of ASD with MR and Ostium primum defect alone cannot produce such murmur and in question it is already mentioned that the patient is having ASD, Floppy mitral valve should be the answer.

“Presence of pansystolic murmur of mitral regurgitation (MR) in a patient with ASD suggests the presence of ostium primum defect with cleft mitral laeflet or floppy mitral valve with mitral valve prolapsed”

“ECG shows right axis deviation in ostium secundum ASD and extreme left axis deviation in ostium primum ASD”

“Clinical presentation of ostium primum is similar to ostium secundum except that there may be a mitral systolic murmur due to MR and ECG shows left axis deviation”

Physostigmine is effective in the treatment of central anticholinergic toxicity caused by overdoses of atropine or scopolamine.

In addition, it reverses some of the central nervous system depression and delirium associated with use of

benzodiazepines and volatile anesthetics. 

Tissues most sensitive to atropine are the salivary, bronchial, and sweat glands. Secretion of acid by the gastric parietal cells is the least sensitive.

• Other factors that influence the cholinergic tone of various organs.
• Variations in synaptic gaps

• Plants and mushrooms containing anticholinergic alkaloids include
  • Jimsonweed (Datura stramonium)
  • Deadly nightshade (Atropa belladonna)
  • Fly agaric (Amanita muscaria)
• The root of Atropa belladonna contains 82-97% of hyoscyamine, 3-15% atropine, and up to 2.5% scopolamine.
• Anticholinergic agents competitively antagonize the effects of acetylcholine at peripheral muscarinic and central receptors.

Also know: LES pressure is higher in the supine position than in the upright position.

Tropicamide is the quickest (20-40min) and shortest acting (3-6hours) mydriatic.

The commonly used mydriatics comprise two groups of drugs:

(i) Parasympatholytic, which cause pupillary dilatation and paralysis of accommodation by rendering the sphincter pupillae and ciliary muscles insensitive to acetylcholine.

(2) Sympathomimetic, which imitate or potentiate the action of adrenaline and produce pupillary dilatation but no cycloplegia.

• These drugs potentiate the action of parasympatholytic drugs. 

Most mydriatics reach their maximal effect by 30 to 6o minutes, although in children and people with deeply pigmented irides this may take longer.

Parasympatholytic drugs

•  ATROPINE (0.5 to 2 per cent.) The most powerful cycloplegic available, producing mydriasis and cycloplegia lasting up to 2 weeks. It can be temporarily reversed by I: 1OO intracameral acetylcholine.
• Indications: (a) Treatment of anterior uveitis. (b) Refracting children under 5 years of age. 

(2) OXYPHENONIUM (Antrenyl) (and 5 per cent.)

• Produces a powerful mydriasis lasting up to 4 days and cycloplegia lasting up to I2 days. 
• Indications: Useful substitute for atropine in sensitive patients. 

(3) HYOSCINE (Scopolamine) (0.25 and 0.5 per cent.)

• Produces a powerful mydriasis and cycloplegia lasting up to 5 days. 
• Indications: Treatment of anterior uveitis in atropine-sensitive patients. 

(4) HOMATROPINE (1 to 5 per cent.)

• Mydriasis lasts up to 2 days. 
• It does not cause complete cycloplegia in children. 
• Augmented by cocaine and reversed by eserine. 
• Indications: (a) Ophthalmoscopy. (b) Preoperatively for cataract extraction. 

(5) EUCATROPINE (Euphthalmine) (5 and 10 per cent.) Effective mydriatic lasting only 4 hours, producing little cycloplegia. 

• Indications: (a) Ophthalmoscopy. (b) Provocative test in suspected closed-angle glaucoma. 

(6) CYCLOPENTOLATE (Mydrilate, Cyclogyl) (0.5 to 2 per cent.) Short-acting mydriatic and cycloplegic.

• Indications: (a) Refraction. Maximal cycloplegia occurs within 45 minutes and persists for 30 minutes. Complete recovery occurs within 24 hours but can be reduced to 6 hours by 2 per cent. pilocarpine. 
• (b) Ophthalmoscopy. Maximal mydriasis within 30 minutes. Particularly valuable in patients with heavily pigmented irides. 
• (c) Preoperatively for cataract extraction. 

(7) TROPICAMIDE (Mydriacyl) (i and 2 per cent.) Rapidly-acting mydriatic and cycloplegic reaching its maximal activity in 20 minutes and lasting 6 hours. Indications: (a) Refraction in adults. Maximal cycloplegia persists for only 20 minutes. (b) Ophthalmoscopy. (c) Preoperatively for cataract extraction.

(8) LACHESINE (E3) (I and 2 per cent.) Weak mydriatic and cycloplegic lasting 6 hours.

• Restlessness and excited behavior with 
• Dryness and flushing of the skin of the face
• Dry mouth
• Fever
• Inhibition of sweating
• Tachycardia 

D i.e. Glucoma

Atropine is contraindicated in narrow angle glucomaQ.

Atropine is used as antidote for various poisons with cholinergic symptoms as – Anticholine Esterase (Organophosphorus) poisoning, Neostigmine / Pyridostigmine / Plzysostigmine overdose, Mushroom poisoningQ

Ans. ‘d’ i.e., Is a competitive antagonist of acetylcholine

• Atropine acts as a competitive antagonist at muscarinic receptors.
• It has no activity on nicotinic receptors and has nothing to do with Ach release.

Ans. is ‘c’ i.e., Bradycardia

o Atropine is an anticholinergic drug and thus causes tachycardia (not bradycardia)

Ans. is ‘a’ i.e., Increase bowel sound; ‘c’ i.e., Hypotension

o Whenever there is peristalatic activity, there will be bowel sound —) Peristalasis causes movement of gases (that are present in the bowel) which results in bowel sound.

o When there is paralysis of bowel smooth muscles (paralytic ileus), bowel sound will be absent.

o Now you can easily understand that

i) Drugs that increase peristalasis (e.g. cholinergic drugs) will increase bowel sound.

ii) Drugs that decrease peristalasis (e.g. anticholinergic drugs —) atropine) will decrease bowel sound. About other options

There are no changes in blood pressure or cardiac output — Goodman & Gilman Atropine causes tachycardia.

Ans. is ‘b’ i.e., Bronchoconstriction

Atropine causes bronchodilation.

Ans. is ‘d’ i.e., Miotic

CLINICAL USES OFATROPINE

Remember – ATROPA

A As mydriatic – cycloplegic

T —> ‘Traveller’s diarrhoea

R —> Rapid (early) onset mushroom poisoning

0 —> Organophosphate poisoning

P —> Preanaesthetic medication

A Arrhythmias (brady-arrhythmias)

Atropine is also used with neostigmine in mysthenia gravis to decrease anti,nuscarinic side effects of neostigmine —› As atropine blocks muscarinic receptors, use of atropine prevents muscarinic side effects of neostigmine, while neostigmine retains its benficial effects in mysthenics which are due to nicotinic receptors.

Ans. is ‘c’ i.e., Acts on central and peripheral cholinergic receptors

o In organophosphate poisoning, atropine counteracts the peripheral muscarinic symptoms and at higher doses central effects as well.

o Atropine does not reverse nicotinic action i.e., peripheral muscular paralysis.

Ans. is ‘c’ i.e., Muscarinic receptor inhibition

Oxybutnin

o Oxybutynin is an anticholinergic drug.

o It is relatively selective for M₃ receptors, so it has selective action on urinary bladder.

• Because of its vesicoselective action it is used for detrusor instability and urinary incontinence.

Ans. is ‘a’ i.e., Pirenzepine

Pirenzepine is a selective M₁  anti-cholinergic & usual doses inhibit acid secretion by 40-50%.

Ans. is ‘c’ i.e., Domperidone

o Drugs used are :

a)         Anticholinergics —> Hyoscine (Scopolamine), Dicyclomine.

b)      H_l-antihistaminic —> Promethazine, cyclizine, meclizine, cinnarizine, etc.

o Hyoscine (scopolamine) is the most effective drug for motion sickness.

About option ‘c’

o Domperidone is a prokinetic drug and acts by D₂ blockade. It is ineffective in motion sickness as vestibular pathway does not involve dopaminergic link.

D i.e. Pirenzepine

D i.e. 1% Atropine ointment

A i.e. Atropine sulphate ointment

 Treatment 

• This is aimed at: suppressing inflammation in the eye, and relieving pain in anterior uveitis; preventing damage to ocular structures, particularly to the macula and the optic nerve, which may lead to permanent visual loss.

 Steroid therapy:

•  In anterior uveitis, dilating the pupil relieves the pain from ciliary spasm and prevents the formation of posterior synechiae by separating it from the anterior lens capsule.
•  Synechiae otherwise interfere with normal dilation of the pupil. Dilation is achieved with mydriatics, e.g. cyclopentolate or atropine drops.
•  Atropine  (most potent) has a prolonged action lasting weeks. An attempt to break any synechiae that have formed should be made with initial intensive cyclopentolate and phenylephrine drops. 
•  A subconjunctival injection of mydriatics may help to break resistant synechiae.

C i.e. Iridocyclitis

• Steroid > Atropine is drug of choice for acute iridocyclitis (anterior uveitis).Q

Atropine is contraindicated in glucomas where as pilocarpine is contraindicated in anterior uveitis. Q

Ans. Irregular dilatation of pupil with atropine in the presence of segmental posterior synechiae

Ans: B i.e. Hyoscine

• Metoclopramide is an effective and popular drug for many types of vomiting – postoperative, drug induced, disease associated (migraine), radiation sickness, etc.
• Hyoscine is the most effective antiemetic drug for motion sickness and is not effective in vomiting of other etiologies
• Ondansetron belongs to a new class of antiemetic drugs developed to control cancer chemotherapy/radiotherapy induced vomiting
• Neuroleptics/antipsychotics have broad spectrum antiemetic action effective in drug induced and post-anaesthetic nausea and vomiting etc.

Ans. Atropine

Ans. is `d’ i.e., Hyoscine

Motion sickness is more easily prevented than cured.

Transdermal hyoscine (scopolamine) is the best agent for the prevention of /notion sickness.

Antihistamines can also be used for prevention.

Ans. is ‘a’ i.e., Valethamate

Anticholinergic drugs

1. Natural alkaloids Atropine, Hyoscine (Scopolamine).
2. Semisvnthetic derivatives Homatropine, Atropine methonitrate, Hyoscine butyl bromide, Ipratropium bromide, Tiotropium bromide.
3. Synthetic compounds

a) Mydriatics : Cyclopentolate, Tropicamide.

b) Antisecretory-antispasmodics :

1. Quaternary compounds : Propantheline, Oxypheonium, Clidinium, Pipenzolate methyl bromide, Isopropamide. Glycopyrolate.
2. Tertiary amines : Dicyclomine, Valethamate, Pirenzepine

c) Vasicosective : Oxbutynin, Flavoxate, Toltcrodine.

d) Antiparkinsonian : Trihexphenidyl (Benzhexol), Procyclidine. Biperiden.

Ans. b. Glycopyrrolate

Glycopyrrolate is a synthetic quaternary anticholinergic drug, which doesn’t cross the blood brain barrier and completely lacks central effects.

Glycopyrrolate is a synthetic quaternary anticholinergic drug, which doesn’t crosses the blood brain barrier and completely lacks central effects.

Glycopyrrolate

• Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation.
• It diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions^Q
• Glycopyrrolate antagonizes muscarinic symptoms° (e.g., bronchorrhea, bronchospasm, bradycardia, and intestinal hypermotility) induced by cholinergic drugs such as the anticholinesterases.
• The highly polar quaternary ammonium group of glycopyrrolate limits its passage across lipid membranes, such as the blood-brain barrier^Q

Ans. is ‘c’ i.e., Hyoscine 

“Transdermal patches ofNTG, fentanyl, nicotine and estradial are available in India, where as those of isosorbide dinitrate, hyoscine and clonidine are marketed elsewhere”. — KDT